There is now convincing evidence to suggest that the Epstein-Barr virus (EBV) is an important factor in the pathogenesis of HIV-related Hodgkin's disease (HD). Over the last many years two powerful tools, irradiation and multi-agent chemotherapy have emerged as the mainstays for the treatment of HIV-related HD. However, these antineoplastic treatments display high levels of toxicity and induce immunosuppression which further compromises the immunodeficiency of HIV-infected patients and facilitate the onset of opportunistic infections and/or evolution of HIV infection. Due to these limitations, additional forms of treatment have been sought. One approach is to stimulate the patient's own cytotoxic T lymphocytes (CTL) against EBV antigens present in the tumor cells. Preliminary studies with adoptive transfer of EBV-specific CTLs in a small cohort of non-HIV HD patients have indicated a transient improvement in clinical and immunological parameters. However, application of such immunotherapeutic protocols in HIV patients is often constrained by the regulatory protocols and expensive reagents to produce custom-designed CTL lines. The presence of EBV in the malignant cells provides a unique opportunity to develop therapeutic vaccines based on viral epitopes and thus provides a more advantageous approach when treating a larger cohort of patients. In the present study, we propose to develop a CTL epitope-based therapeutic vaccine and test the efficacy of this vaccine in a transgenic preclinical setting which is designed to reflect the immunological setting of HIV patients. This vaccine will be based on the "polyepitope" technology and exploits a novel replication deficient adenovirus expression system which has recently been approved for human use. The long-term aim of this project is to develop a rational basis for the delivery of a curative EBV-specific CTL immunity to not only in HIV patients with HD patients but also for non-HIV HD. [unreadable] [unreadable] [unreadable]